Hyperinsulinism-hyperammonemia syndrome in two Peruvian children with refractory epilepsy.

OBJECTIVES: Congenital hyperinsulinism (HI) is a heterogeneous clinical disorder with great variability in its clinical phenotype, and to date, pathogenic variants in 23 genes have been recognized.  Hyperinsulinism-hyperammonemia syndrome (HI/HA) is the second most frequent cause of this disease that shows an autosomal dominant pattern and is caused by an activating mutation of the GLUD1 gene, which responds favorably to the use of diazoxide. HI/HA syndrome presents with fasting hypoglycemia; postprandial hypoglycemia, especially in those with a high protein content (leucine); and persistent mild hyperammonemia. Neurological abnormalities, in the form of epilepsy or neurodevelopmental delay, are observed in a high percentage of patients; therefore, timely diagnosis is crucial for proper management. CASE PRESENTATION: We report the clinical presentation of two Peruvian children that presented with epilepsy whose genetic analysis revealed a missense mutation in the GLUD1 gene, one within exon 11, at 22% mosaicism; and another within exon 7, as well as their response to diazoxide therapy. To the best of our knowledge, these are the first two cases of HI/HA syndrome reported in Peru. CONCLUSIONS: HI/HA syndrome went unnoticed, because hypoglycemia was missed and were considered partially controlled epilepsies. A failure to recognize hypoglycemic seizures will delay diagnosis and adequate treatment, so a proper investigation could avoid irreversible neurological damage.

Association of Central Precocious Puberty with a Rare Presentation of Schimmelpenning-Feuerstein-Mims Syndrome in a Peruvian Girl.

Schimmelpenning-Feuerstein-Mims syndrome (SFM), an epidermal nevus syndrome characterized by skin lesions, has an estimated incidence of 1 per 10 000 live births. Nevus sebaceous, the most common cutaneous lesion, and verrucous nevus, the less frequent lesion, are coupled with a wide range of extracutaneous manifestations. As part of these manifestations, rarely, central precocious puberty can arise. We report the case of a 1-year-5-month-old girl who presented to the Endocrinology and Metabolism Department with breast enlargement that began at one year of age, growth of pubic and axillary hair three months later, and vaginal bleeding that occurred five months later. During clinical examination, melanocytic nevi, with a diameter ranging from 3 to 5 mm, were noted on the face. Verrucous nevi of variable size with a tendency for coalescence following the lines of Blaschko and melanocytic nevi with a diameter ranging from 3 to 6 mm were observed on the right hemibody and on the left hemibody, respectively. Right asymmetry of the lower extremities was observed. Laboratory findings showed a significant increase in the levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) after the gonadotropin-releasing hormone (GnRH) stimulation test; additionally, imaging demonstrated advanced bone age and pubertal changes in the internal genitals. Analyses of the H-RAS, K-RAS, and N-RAS genes in the blood and in the skin were performed, and a missense mutation in exon 2 of the gene, H-RAS c37G > C (p.G13R), was detected in the latter. Treatment with triptorelin, a GnRH analog, was initiated, and it gave good clinical response. Epidermal nevus syndrome has a wide and variable systemic involvement. Thus, it is important to consider the development of precocious puberty for a prompt diagnosis and to strategize a multidisciplinary approach from the beginning.

Factores predictivos de la microalbuminuria en pacientes pediátricos con diabetes mellitus tipo 1 (DMt1) / Microalbuminuria predictive factors in pediatric patients with type 1 diabetes mellitus (type 1 DM)

La nefropatía constituye la complicación más grave de la diabetes mellitus tipo 1 (DMt1) siendo una de las manifestaciones iniciales la microalbuminuria. Objetivos: Determinar el comportamiento de los factores epidemiológicos, clínicos y bioquímicos en el desarrollo de microalbuminuria en pacientes con DMt1. Diseño: Estudio de casos y controles. Lugar: Servicio de Endocrinología del Instituto Nacional de Salud del Niño, Lima, Perú. Participantes: Pacientes diabéticos tipo 1 menores de 18 años. Intervenciones: Se estudió 64 pacientes portadores de DMt1, 22 con microalbuminuria y 42 sin esta manifestación, que constituyeron los casos y controles respectivamente. Se consignó como factores epidemiológicos la edad al diagnóstico, tiempo de evolución, género, antecedentes familiares de diabetes, nefropatía, dislipidemia, hipertensión arterial; como factores clínicos, el estado nutricional, desarrollo puberal (Tanner), presión arterial; y como factores bioquímicos, la hemoglobina glicosilada (HbA1c), microalbuminuria y perfil lipídico. Tanto los casos como los controles fueron seguidos durante un año. El análisis estadístico se hizo mediante pruebas de chi cuadrado, odds ratio y regresión logística, para establecer predominancia de factores. Principales medidas de resultados: Estadio puberal, perfil lipídico y HbA1c. Resultados: Los factores de riesgo hallados fueron la presión arterial diastólica elevada (p=0,037), la pubertad (p=0,008), HbA1c alta (p< 0,0001), hipertrigliceridemia (p= 0,007) y la hipercolesterolemia (p< 0,0001). Conclusiones: La HbA1c elevada, la hipercolesterolemia y la pubertad fueron los factores de riesgo de mayor preponderancia para el desarrollo de microalbuminuria. A fin de prevenir el desarrollo de microalbuminuria, se sugiere buen control metabólico y cuidadoso manejo de la dislipidemia, en especial en pacientes púberes.

Nephropathy constitutes the most serious type 1 diabetes mellitus (type 1 DM) complication and microalbuminuria is the initial manifestation. Objectives: To determine the role of epidemiological, clinical and biochemical factors in the development of microalbuminuria in type 1 DM patients. Design: Case and control study. Setting: Endocrinology Unit, National Institute of Child Health, Lima, Peru. Patients: Subjects less than 18 year-old with type 1 DM. Interventions: Sixty-four type 1 DM patients were studied, 22 patients with microalbuminuria (cases) and 42 patients without it (controls). Epidemiological factors studied were age at diagnosis, time from onset, gender, family history of diabetes, nephropathy, dyslipidemia, and/or hypertension; clinical factors studied were nutritional status, pubertal stage (Tanner method) and blood pressure; biochemical factors were glycated hemoglobin (HbA1c), microalbuminuria and lipid profile. Both cases and controls were followed for one year. Statistical analysis used chi square, odds ratio and multiple logistic regression calculations to determine main risk factors. Main outcome measures: Pubertal stage, lipid profile and HbA1c. Results: Risk factors determined were high diastolic blood pressure (p=0.037), puberty (p=0.008), high HbA1C (p<0.0001), hypertriglyceridemia (p=0.007), and hypercholesterolemia (p<0.0001). Conclusions: Elevated HbA1c, hypercholesterolemia and puberty were the more important risk factors for development of microalbuminuria. Main measures to prevent development of microalbuminuria were good metabolic control and good management of dyslipidemia, especially in pubertal patients.

Factores predictivos de la microalbuminuria en pacientes pediátricos con diabetes mellitus tipo 1 / Facktors risk of microalbuminuria in pediatric patients whith diabetes Mellitus, Type 1

Objetivo: Determinar el comportamiento de los factores epidemiológicos, clínicos y bioquímicos en el desarrollo de microalbuminuria en los pacientes diabéticos tipo 1 que se atienden en el Programa de Atención Integral del Niño Diabético (PAINDI) del Servicio de Endocrinología del Instituto Nacional de Salud del Niño. Metodología: Se realizó un estudio analítico observacional de tipo casos y controles. Se incluyeron a los pacientes diabéticos tipo 1 menores de 18 años con y sin microalbuminuria atendidos en el Servicio de Endocrinología de Junio 1999 a Mayo 2009, consignando los probables factores epidemiológicos (edad al momento del diagnóstico, tiempo de evolución de la enfermedad, género, antecedentes familiares de diabetes, nefropatía, dislipidemia y/o hipertensión arterial), clínicos (estado nutricional, estadio puberal y presión arterial) y bioquímicos (HbA1c, microalbuminuria y perfil lipídico) asociados al desarrollo de microalbuminuria. Los casos fueron aquellos pacientes con diabetes mellitus tipo 1 (DM1) con mínimo un año de evolución de la enfermedad, que presentaron microalbuminuria y los controles fueron los que no la presentaron. Se utilizó la prueba chi cuadrado y el cálculo de los Odds Ratio. Se realizó el análisis multivariado a través de la regresión logística para establecer el factor predominante en el desarrollo de microalbuminuria: Se consideró un p < 0.05 como significativo. Resultados: Participaron en el estudio 64 pacientes menores de 18 años con DM1...

Objective: To determine the epidemiological, clinical and biochemical risk factors for the development of microalbuminuria in type 1 diabetic patients who are attended in the PAINDI of the National Institute of Child Health. Methodology: An observational, analytical, case control study was carried out. The subjects were type 1 diabetes patients of age under 18 years who were treated at the Endocrinology Department from June, 1999 to May, 2009. Epidemiological risk factors (age at diagnosis, duration of illness, gender, background family history of diabetes, nephropathy, dyslipidemia and/or hypertension), clinical risk factors (nutritional status, pubertal stage, blood pressure) and biochemical risk factors (glycated hemoglobin, microalbuminuria and lipid profile) were studied. The cases were patients with T1DM who had microalbuminuria and at least one year of disease. Controls were diabetic patients without microalbuminuria. The statistical analysis was carried out calculating the Chi square and odds ratio. Multivariate analysis was performed through logistic regression to establish the main risk factor for the development of microalbuminuria. A p < 0.05 was considered statistically significant. Results: 64 patients with type 1 diabetes under 18 years were studied...